The focus of this thesis was to investigate developmental neurotoxic effects of different persistent and non-persistent environmental pollutants, alone or in binary mixtures, when exposure occurs during a critical period of brain development, in mice. The compounds investigated included a perfluorinated compound, perfluorohexane sulphonate (PFHxS), and four different pesticides, endosulfan, cypermethrin, chlorpyrifos and carbaryl. Both persistent and non-persistent pollutants are detected in the environment and in humans, which shows that exposure to these compounds is occurring in real life. Humans can therefore be exposed to various pollutants during their whole lifetime, starting from the gestational period to adulthood. Furthermore, exposure to environmental pollutants is rarely exclusive to a single compound, but rather occurs through combinations of various pollutants present in the environment. Exposure to environmental pollutants during human brain development have been suggested to be a possible cause for neuropsychiatric disorders, such as autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). Previous studies have shown that chemicals can induce irreversible disorders in brain function when exposure to these chemicals occurs during a critical defined period of the brain development known as the brain growth spurt (BGS). The BGS is characterized by a rapid growth and development of the immature brain. In humans, and mice, this period also overlaps the lactation period indicating that newborns and toddlers can be exposed via mothers’ milk as well. This thesis has shown that a single oral exposure to PFHxS, endosulfan, cypermethrin, chlorpyrifos or carbaryl can induce developmental neurotoxic effects in mice, when exposure occurs during a critical period of brain development. These effects are manifested as persistent altered adult spontaneous behavior in a novel home environment, modified habituation, altered susceptibility of the cholinergic system and changed levels of neuroproteins in the mouse brain. Furthermore, a single neonatal co-exposure to a binary mixture of carbaryl/chlorpyrifos or PFHxS/endosulfan can interact and exacerbate the adult behavioral effects. These effects were seen at dosages were the single compound did not elicit a response or induced a much weaker behavioral effect. This indicates that risk assessments conducted on single compounds might underestimate interaction effects of mixtures when co-exposed.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / The storage and handling points of agricultural sprayers on farms are a contamination point source of punctual contamination in case of accidental spills of concentrated pesticide and / or leaks, among others. In order to avoid possible environmental contaminations, since the decade of 90 s have been developed biobed systems, where the handling of pesticides as well as agricultural implements washing are discharded on a mixture of straw, soil and peat (biomix). This mixture has the ability to retain and subsequently biodegrade pesticides. In this study was validated an analytical method applied for routine analysis to determine the organophosphate pesticide chlorpyrifos in biobeds. The method is based on 5 g sample extraction with 30 mL of acetone acidified with phosphoric acid 98:1:1 (v/v/v). After homogenization, centrifugation and filtration, 125 μL of the extract was evaporated and reconstituted in 5 mL of methanol acidified with 0.1% acetic acid. The analysis was performed on a liquid chromatographic system coupled to a tandem mass spectrometer (UPLC-MS/MS). The validation parameters evaluated were calibration curve linearity (r2), accuracy (spike and recovery %), limits of detection (LOD) and quantification (LOQ) of the instrument and the method, precision (RSD%) and matrix effect. To the linearity study analytical solutions were prepared in organic solvent and matrix extract at 0.1; 0.5; 1; 5; 20; 100; 250 ng mL-1. The recovery study was conducted on samples spiked at three concentrations (2, 10 and 50 mg kg-1) with seven replicates (n = 7) for each concentration and the values obtained were between 96 and 115% with RSD values lower than 20 % for all three concentration levels studied. The real LOQ obtained was 2 mg kg-1 and the matrix effect observed was lower than ± 20%, which demonstrates that there is not considerable suppression or enhancement in the analyte signal. The biobed system efficiently degraded chlorpyrifos in both 1) simulation of accidental spillage and 2) application of diluted pesticide solution. In the latter case, all the values obtained at the final sampling time (14 months) were below the real LOQm. / Os pontos de estocagem e manuseio de pulverizadores agrícolas em fazendas são uma fonte de contaminação pontual no caso de derrames acidentais do agrotóxico concentrado e/ou vazamentos. A fim de evitar possíveis contaminações ambientais, desde a década de 90 tem sido desenvolvidos sistemas de camas biológicas, onde o manejo de agrotóxicos bem como a lavagem de implementos agrícolas é feito sobre uma mistura de palha, solo e turfa. Esta biomistura tem a capacidade de reter e posteriormente biodegradar os agrotóxicos. Neste estudo foi validado um método para análises de rotina para determinação do agrotóxico organofosforado clorpirifós em camas biológicas. O método baseia-se na extração de 5 gramas de amostra com 30 mL de uma solução de acetona acidificada com ácido fosfórico 98:1:1 (v/v/v). Após homogeneização, centrifugação e filtração, 125 μL do extrato foi evaporado e reconstituído em 5 mL de metanol acidificado com 0,1% de ácido acético. A análise foi realizada em um sistema de cromatografia líquida acoplado a um espectrômetro de massas tandem (UPLC-MS/MS). Os parâmetros de validação avaliados foram linearidade da curva analítica (r2), exatidão (fortificação e recuperação em %), limites de detecção (LOD) e quantificação (LOQ) do instrumento e do método, precisão (RSD %) e efeito matriz. Para o estudo de linearidade as soluções analíticas foram preparadas em solvente orgânico e em extrato de matriz, a 0,1; 0,5; 1; 5; 20; 100; 250 ng mL-1. O estudo de recuperação foi realizado em amostras fortificadas em três concentrações (2, 10 e 50 mg kg-1) repetido sete vezes (n=7) para cada concentração. Os valores obtidos ficaram entre 96 e 115% com valores de RSD inferiores a 20% para os três níveis de concentração estudados. O LOQ real obtido foi 2 mg kg-1. O efeito matriz observado foi inferior a ± 20%, o que demonstra que não há supressão ou aumento considerável no sinal do analito. O sistema de camas biológicas foi eficiente para a degradação de clorpirifós em ambos 1) simulação de derrame acidental e 2) aplicação de solução diluída do agrotóxico. Neste último caso, todos os valores obtidos ao final das etapas de amostragem (14 meses) ficaram abaixo do LOQm real.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Pesticides are substances used in agricultural areas and public health programs to control pests and disease vectors. Among pesticides, organophosphates (OPs) are considered the most toxic to vertebrates. Diphenyl diselenide [(PhSe)2] is an organoselenium compound that presents pharmacological activities, among that the antioxidant effect. Therefore, the aim of this study was to evaluate the pharmacological effects of (PhSe)2 in acute models of toxicity induced by chlorpyrifos (CPF) and acephate (AC) in rats, as well as to investigate the hyperglycemic and hyperlipidemic effects of CPF which has not been described. In the first experimental protocol (article 1), the effect of (PhSe)2 on hepatic and hematological toxicity induced by CPF in rats was evaluated. The animals were pre-treated by intragastric route (p.o.) with (PhSe)2 (5 mg/kg) once a day for 7 days. On the 8th and 9th days, (PhSe)2 (5 mg/kg; p.o.) was administered to rats 30 min prior to subcutaneous (s.c.) injection of CPF (50 mg/kg). Twenty-four hours after the last CPF injection, rats were killed. The aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) activities were determined in plasma of rats. Lipid peroxidation, protein carbonyl and non-protein thiol (NPSH) levels as well as catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and gluthatione S-transferase (GST) activities were determined in livers of rats. Hematologic parameters were also assayed. CPF caused an increase in AST, ALT and LDH activities, an increase in lipid peroxidation and protein carbonyl levels, a decrease in NPSH levels and an inhibition of CAT, GPx, SOD and GST activities. In addition, CPF exposure caused hematologic toxicity, evidenced mainly by a decrease in total leukocytes levels. (PhSe)2 protected against toxic effects induced by CPF in rats. Moreover, (PhSe)2 increased per se NPSH levels and GST activity in livers of rats. In the second experimental protocol (article 2), the effect of (PhSe)2 on metabolic disorders induced by AC in rats was investigated. (PhSe)2 (10 or 30 mg/kg; p.o.) was administered to rats 1 hour prior to AC administration (140 mg/kg; p.o.). Two hours after AC administration, rats were killed. Glucose and corticosterone levels as well as the lipid status were determined in plasma of rats. Cardiovascular risk factor and the atherogenic index were calculated. Glycogen levels as well as tyrosine aminotransferase (TAT) and glucose-6-phosphatase (G6Pase) activities were determined in livers of rats. Cerebral acetylcholinesterase (AChE) activity was assayed. AC induced an increase in glucose, corticosterone and triglycerides (TG) levels, an increase in TAT and G6Pase activities and an inhibition of AChE activity. The cardiovascular risk factor [(TG/ high density lipoprotein (HDL)] was increased in AC exposed rats. (PhSe)2 attenuated these alterations, except for the increase of corticosterone levels and AChE activity inhibition. In the third experimental protocol (article 3), the hyperglycemic and hyperlipidemic effects of CPF in rats were investigated. The mechanisms involved in hyperglycemia induced by CPF were also studied. CPF was administered once to rats at the dose of 50 mg/kg, s.c. Animals were killed at 2, 4, 8, 12 e 24 hours after CPF administration. Glucose and corticosterone levels as well as lipid status and paraoxonase-1 (PON-1) activity were determined in plasma of rats. Cardiovascular risk factors and the atherogenic index were calculated. Glycogen levels as well as TAT and G6Pase activities were determined in livers of rats. Cerebral AChE activity was assayed. CPF caused an increase in glucose, glycogen, corticosterone, TG and low density lipoprotein (LDL) levels, an increase in TAT and G6Pase activities, a decrease in HDL levels and PON-1 activity and AChE activity inhibition. The cardiovascular risk factors and atherogenic index were increased in CPF exposed rats. The results of the present study demonstrated that (PhSe)2 protected against toxic effects induced by CPF and AC in rats. CPF exposure caused hyperglycemia and hyperlipidemia in rats. The gluconeogenesis pathway activation is involved in the hyperglycemic effect caused by CPF. Considering that the crescent use of OPs worldwide has been the cause of many severe human poisoning cases, the results of the present work are of great importance, since that (PhSe)2 may represent an alternative to alleviate the OPs-induced toxicity. / Os agrotóxicos são substâncias empregadas nas áreas agrícolas e em programas de saúde pública, para o controle de pragas e vetores que transmitem doenças. Dentre os agrotóxicos, os inseticidas organofosforados (OFs) são considerados os mais tóxicos aos vertebrados. O disseleneto de difenila [(PhSe)2] é um composto orgânico de selênio para o qual já foram descritas diversas propriedades farmacológicas, entre elas a atividade antioxidante. Dessa forma, este trabalho teve como objetivos avaliar os efeitos farmacológicos do (PhSe)2 em modelos de toxicidade aguda induzida por clorpirifós (CPF) e acefato (AC) em ratos, bem como, avaliar os efeitos hiperglicêmico e hiperlipidêmico do CPF, os quais não estão descritos na literatura. No primeiro protocolo experimental (artigo 1), avaliou-se o efeito do (PhSe)2 na toxicidade hepática e hematológica induzida por CPF em ratos. Os animais foram pré-tratados com (PhSe)2 (5 mg/kg) pela via intragástrica (p.o.) uma vez ao dia durante 7 dias. No 8º e 9º dias o (PhSe)2 (5 mg/kg; p.o.) foi administrado 30 min antes da administração subcutânea (s.c.) de CPF (50 mg/kg). Os animais foram mortos vinte e quatro horas após a última administração de CPF. A atividade das enzimas aspartato aminotransferase (AST), alanina aminotransferase (ALT) e lactato desidrogenase (LDH) foram determinadas no plasma dos ratos. Os níveis de peroxidação lipídica, carbonilação de proteínas e tióis não-protéicos (SHNP), bem como a atividade das enzimas catalase (CAT), superóxido dismutase (SOD), glutationa peroxidase (GPx), glutationa redutase (GR) e glutationa S-transferase (GST) foram determinados no fígado dos ratos. Os parâmetros hematológicos também foram analisados. O CPF causou aumento da atividade das enzimas AST, ALT e LDH, aumento dos níveis de peroxidação lipídica e carbonilação de proteínas, diminuição dos níveis de SHNP e inibição das enzimas CAT, GPx, SOD e GST. Além disso, a exposição ao CPF causou toxicidade hematológica, evidenciada principalmente pela diminuição dos níveis de leucócitos totais. O (PhSe)2 protegeu contra os efeitos tóxicos induzidos pelo CPF em ratos. Além disso, o (PhSe)2 aumentou per se os níveis de SHNP e a atividade da GST no fígado dos ratos. No segundo protocolo experimental (artigo 2), investigou-se o efeito do (PhSe)2 nos distúrbios metabólicos induzidos por AC em ratos. O (PhSe)2 (10 ou 30 mg/kg; p.o.) foi administrado aos animais 1 hora antes da administração de AC (140 mg/kg; p.o.). Os animais foram mortos duas horas após a administração de AC. Os níveis de glicose e corticosterona bem como o perfil lipídico foram determinados no plasma dos ratos. Os fatores de risco cardiovascular e o índice aterogênico foram calculados. Os níveis de glicogênio bem como a atividade das enzimas tirosina aminotransferase (TAT) e glicose-6-fosfatase (G6Pase) foram analisados no fígado dos ratos. A atividade da acetilcolinesterase (AChE) cerebral também foi determinada. O AC causou aumento dos níveis de glicose, corticosterona e triglicerídios (TG), aumento da atividade das enzimas TAT e G6Pase e inibição da AChE. O fator de risco cardiovascular [(TG/lipoproteína de alta densidade (HDL)] aumentou nos ratos expostos ao AC. O (PhSe)2 atenuou essas alterações, exceto para o aumento dos níveis de corticosterona e para a inibição da AChE. No terceiro protocolo experimental (artigo 3), investigou-se o efeito hiperglicêmico e hiperlipidêmico do CPF em ratos. Também foram estudados os mecanismos envolvidos no efeito hiperglicêmico do CPF. O CPF foi administrado uma única vez na dose de 50 mg/kg, s.c.. Os animais foram mortos em diferentes tempos após a administração de CPF (2, 4, 8, 12 e 24 horas). Os níveis de glicose e corticosterona bem como o perfil lipídico e a atividade da paraoxonase-1 (PON-1) foram determinados no plasma dos ratos. Os fatores de risco cardiovascular e o índice aterogênico foram calculados. Os níveis de glicogênio bem como a atividade das enzimas TAT e G6Pase foram analisados no fígado dos ratos. A atividade da AChE cerebral também foi determinada. O CPF causou aumento dos níveis de glicose, glicogênio, corticosterona, TG e lipoproteína de baixa densidade (LDL), aumento da atividade das enzimas TAT e G6Pase, diminuição dos níveis de HDL e da atividade da PON-1 e inibição da atividade da AChE. Os fatores de risco cardiovascular e o índice aterogênico aumentaram nos animais expostos ao CPF. Os resultados do presente trabalho demonstraram que o (PhSe)2 protegeu contra a toxicidade induzida por CPF e AC em ratos. A exposição ao CPF causou hiperglicemia e hiperlipidemia em ratos. A ativação da via da gliconeogênese está envolvida no efeito hiperglicêmico causado pelo CPF. Considerando-se que a exposição aos OFs é cada vez mais freqüente e que é a causa de diversas doenças, os resultados deste trabalho são de grande importância, uma vez que o (PhSe)2 pode representar uma alternativa para atenuar a toxicidade causada pelos OFs.

No description available.

Thesis (MTech (Chemical Engineering))--Peninsula Technikon, Cape Town, 2003 / The monitoring of pesticide contamination in surface and groundwater is an essential aspect of an assessment of the potential environmental and health impacts of widespread pesticide use. Previous research in three Western Cape farming areas found consistent (37% to 69% of samples) pesticide contamination of rural water sources. However, despite the need, monitoring of pesticides in water is not done due to lack of analytical capacity and the cost of analysis in South Africa. The Solid Phase Microextraction (SPME) sampling method has been developed over the last decade as a replacement for solvent-based analyte extraction procedures. The method utilizes a short, thin, solid rod of fused silica coated with an absorbent polymer. The fibre is exposed to the pesticide contaminated water sample under vigorous agitation. The pesticide is absorbed into the polymer coating; the mass absorbed depends on the partition coefficient of the pesticide between the sample phase and the polymeric coating, the exposure time and factors such as agitation rate, the diffusivity of the analyte in water and the polymeric coating, and the volume and thickness of the coating. After absorption, the fibre is directly inserted into the Gas Chromatograph (GC) injection port for analysis. For extraction from a stirred solution a fibre will have a boundary region where the solution moves slowly near the fibre surface and faster further away until the analyte is practically perfectly mixed in the bulk solution by convection. The boundary region may be modelled as a layer of stationary solution surrounded by perfectly mixed solution.

Submitted by Luciana Ferreira (lucgeral@gmail.com) on 2016-09-16T15:27:12Z No. of bitstreams: 2 Dissertação - Marcia Felipe Mendes - 2016.pdf: 3733938 bytes, checksum: a83e0262d1671e990c617cd0061f8d2f (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2016-09-16T15:27:41Z (GMT) No. of bitstreams: 2 Dissertação - Marcia Felipe Mendes - 2016.pdf: 3733938 bytes, checksum: a83e0262d1671e990c617cd0061f8d2f (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2016-09-16T15:27:41Z (GMT). No. of bitstreams: 2 Dissertação - Marcia Felipe Mendes - 2016.pdf: 3733938 bytes, checksum: a83e0262d1671e990c617cd0061f8d2f (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2016-02-26 / Fundação de Amparo à Pesquisa do Estado de Goiás - FAPEG / Because of the toxicological relevance of pesticides introduced into the environment through agricultural practices, it is necessary to develop simple methodologies with low cost, enabling remove these pollutants from the environment, in particular of water intended for human consumption. The adsorption process is an efficient and low cost technique that have wide application. The adsorbent capacity of the leaves of Typha angustifolia L. herbaceous perennial plant belonging to the family Typhaceae, in Brazil it is also popularly known as taboa, was investigated for the removal of pesticides trifluralin, chlorpyrifos and α-endosulfan from aqueous medium. The the analytical method using solid phase extraction (SPE) and chromatography with electron capture detector (GC/ECD) was optimizates and validate. The validation criterions were reached and the analytical methos was considered efficient for trifluralin, chlorpyrifos and α-endosulfan quantification in an aqueous medium, providing credibility to the results obtained in the adsorption experiments. The adsorption capacity of T. angustifolia was evaluated under different parameters: treatment of the material, amount of material, contact time between the plant material and the pesticides solution and concentration of the pesticides solution. The results showed that treatment of the material with distilled water and was satisfactory and, for all doses evaluated the pesticide removal was efficient, with best results obtained at a dose of 3.0 g L-1 , equivalent to 60 mg of adsorbent in 20.0 mL of solution, in which the pesticide removal were between 73 and 80%. The adsorption kinetics of the pesticide by T. angustifolia showed that the adsorption equilibrium was reached in 40 minutes for all pesticides, removing up to 90% and using a very small amount of plant material (3 g L-1 ). The experimental data were evaluated using the kinetic models of pseudo-first order, pseudo-second order and Avrami. One of the limitations encountered in the concentration influence study is the limited solubility of the agrochemical in aqueous medium (between 0.33 and 1.00 mg L-1 ), resulting in the study of a small concentration range in the adsorption experiments. To study the pesticides adsorption mechanism by T. angustifolia material, the experimental data were applied to Langmuir, Freundlich and Sips non-linear isotherms models. Additional tests showed that the adsorption capacity is unaffected when using natural water in the adsorption experiments. The results indicate that the material obtained from of T. angustifolia leaves, has a great potential to be used as an alternative adsorbent material in pesticide contaminated aqueous solution treatment. / Devido à relevância toxicológica dos agrotóxicos introduzidos no ambiente através de práticas agrícolas, torna-se necessário o desenvolvimento de metodologias simples e de baixo custo, que permitam remover esses poluentes do meio ambiente, em especial, das águas destinadas a consumo humano. O processo de adsorção é uma técnica que possui grande aplicação, por ser eficiente e de baixo custo. A capacidade adsorvente das folhas de Typha angustifolia L., planta herbácea perene pertencente à família Typhaceae, no Brasil também conhecida popularmente como taboa, foi investigada para a remoção dos agrotóxicos trifluralina, clorpirifós e α-endossulfam de meio aquoso. Foi realizada a otimização e validação da metodologia analítica de extração em fase sólida (SPE) e determinação por cromatografia gasosa utilizando-se o detector por captura de elétrons (GC/ECD). A metodologia (SPEGC/ECD) atendeu aos critérios de validação estabelecidos e foi eficiente para a quantificação dos agrotóxicos em meio aquoso, fornecendo credibilidade aos resultados obtidos nos ensaios de adsorção. A capacidade de adsorção da T. angustifolia foi avaliada sob diferentes parâmetros: tratamento do material, dose de material, tempo de contato entre o material vegetal e a solução dos agrotóxicos e concentração dos agrotóxicos na solução. Os resultados obtidos mostraram que o tratamento do material com água destilada foi satisfatório e que para todas as doses de adsorvente avaliadas a remoção dos agrotóxicos foi eficiente, sendo obtido um melhor resultado para a dose de 3,0 g L-1 , equivalente a 60 mg de adsorvente para 20,00 mL de solução, onde se obteve remoção entre 73 e 80% dos agrotóxicos. O estudo cinético do processo de adsorção dos agrotóxicos pela T. angustifolia mostrou que o equilíbrio de adsorção foi alcançado em 40 minutos, para todos os agrotóxicos, com remoção de até 90%, utilizando uma dose muito pequena de material vegetal (3 g L-1 ). Os dados experimentais foram avaliados utilizando-se os modelos cinéticos de pseudo-primeira ordem, pseudo-segunda ordem e Avrami. Uma das limitações encontradas no estudo da influência da concentração foi a solubilidade limitada dos agrotóxicos em meio aquoso (entre 0,33 e 1,00 mg L-1 ), que fez com que os ensaios de adsorção fossem avaliados para uma pequena faixa de concentração. Para estudar o mecanismo de adsorção dos agrotóxicos pelo material T. angustifolia, os dados experimentais foram aplicados aos modelos não lineares de Langmuir, Freundlich e Sips. Ensaios adicionais mostraram que a capacidade de adsorção é pouco afetada quando se utiliza água natural obtida em represas nos ensaios de adsorção. Os resultados obtidos indicam que o material vegetal, obtido a partir das folhas de T. angustifolia, possui um grande potencial para ser utilizado como material adsorvente alternativo no tratamento de meio aquoso contaminado com os agrotóxicos trifluralina, clorpirifós e α-endossulfam.

Effects of developmental exposure to chlorpyrifos (CPS) or methyl parathion (MPS) on visuospatial, adaptive fear response, and passive avoidance memory and the signaling mechanisms responsible for these neurocognitive changes were investigated. Using an incremental low dose regimen, rat pups were orally gavaged daily with either corn oil (vehicle), CPS, or MPS from postnatal day 1 (PND1) -PND21. Cholinesterase activity was significantly inhibited with the highest dosages of CPS and MPS for up to 19 days after the last dosages. OP exposure impaired working and reference memory in males whereas in the females, enhancement occurred following CPS exposure. In addition, the adaptive fear response and passive avoidance retention memory was impaired in males whereas differential changes occurred in females. Accordingly, the behavioral deficits observed in males were persistent whereas the enhancement in females was transient. Males were more sensitive to OPs than females in that the medium and high dosages of CPS and MPS produced greater effects in females whereas all dosages of both compounds produced effects in males. Training in the radial arm maze significantly increased protein kinase C gamma (PKC ) expression and activity in the hippocampal membrane fraction of control rats whereas exposure to OPs exhibited a significant decrease in PKC and PKC immunoreactivity in both untrained and trained rats. However, MPS exposed females exhibited a significant increase in PKC expression in the cytosolic fraction but this was not related to improved memory. Reduction of membrane PKC expression and activity and cytosolic PKC expression and activity seemed to be related to visuospatial learning and memory deficits in exposed males but not exposed females. Brain-derived neurotrophic factor (BDNF) gene expression in the hippocampus was significantly increased (60%) in trained control males as compared to untrained control males. In contrast, trained and untrained females exhibited similar levels of BDNF gene expression. However, exposure of both sexes to either CPS or MPS significantly reduced the expression of BDNF in trained rats. In summary, these data indicate that OP exposure induced gender-specific changes in working memory formation and altered PKC isozyme levels/activity and BDNF expression.